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The purpose of this study was to analyze the impact of melatonin on calcium\u2010signaling components under different conditions. In a transfected INS\u20101 cell line overexpressing the human MT2 receptor (<jats:styled-content style=\"fixed-case\">hMT<\/jats:styled-content>2\u2010INS\u20101), melatonin treatment induced even stronger depressive effects on calcium\/calmodulin\u2010dependent kinase 2d and IV (Camk2d, CamkIV) transcripts during 3\u2010isobutyl\u20101\u2010methylxanthine (IBMX) treatment than in normal INS\u20101 cells, indicating a crucial influence of melatonin receptor density on transcript\u2010level regulation. In addition, melatonin induced a significant downregulation of calmodulin (Calm1) in IBMX\u2010treated <jats:styled-content style=\"fixed-case\">hMT<\/jats:styled-content>2\u2010INS\u20101 cells. Long\u2010term administration of melatonin alone reduced CamkIV transcript levels in INS\u20101 cells; however, transcript levels of Camk2d remained unchanged. The release of insulin was diminished under long\u2010term melatonin treatment. The impact of melatonin also involved reductions in CAMK2D protein during IBMX or forskolin treatments in INS\u20101 cells, as measured by an enzyme\u2010linked immunosorbent assay, indicating a functional significance of transcriptional changes in pancreatic islets. Furthermore, analysis of melatonin receptor knockout mice showed that the transcript levels of Camk2d, CamkIV, and Calm1 were differentially influenced according to the melatonin receptor subtype deleted. In conclusion, this study provides evidence that melatonin has different impacts on the regulation of Calm1 and Camk. These calcium\u2010signaling components are known as participants in the calcium\/calmodulin pathway, which plays an important functional role in the modulation of the <jats:italic>\u03b2<\/jats:italic>\u2010cell signaling pathways leading to insulin secretion.<\/jats:p>","DOI":"10.1111\/jpi.12135","type":"journal-article","created":{"date-parts":[[2014,3,20]],"date-time":"2014-03-20T19:03:53Z","timestamp":1395342233000},"page":"439-449","source":"Crossref","is-referenced-by-count":14,"title":["Calcium\u2010signaling components in rat insulinoma <i>\u03b2<\/i>\u2010cells (<scp>INS<\/scp>\u20101) and pancreatic islets are differentially influenced by melatonin"],"prefix":"10.1111","volume":"56","author":[{"given":"Ivonne","family":"Bazwinsky\u2010Wutschke","sequence":"first","affiliation":[{"name":"Institute of Anatomy and Cell Biology Martin Luther University Halle\u2010Wittenberg Halle 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